Department of Integrative Physiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Nagoya University Institute for Advanced Research, Nagoya 464-8601, Japan.
Sci Adv. 2022 Dec 23;8(51):eadd5463. doi: 10.1126/sciadv.add5463.
The bidirectional controller of the thermoregulatory center in the preoptic area (POA) is unknown. Using rats, here, we identify prostaglandin EP3 receptor-expressing POA neurons (POA neurons) as a pivotal bidirectional controller in the central thermoregulatory mechanism. POA neurons are activated in response to elevated ambient temperature but inhibited by prostaglandin E, a pyrogenic mediator. Chemogenetic stimulation of POA neurons at room temperature reduces body temperature by enhancing heat dissipation, whereas inhibition of them elicits hyperthermia involving brown fat thermogenesis, mimicking fever. POA neurons innervate sympathoexcitatory neurons in the dorsomedial hypothalamus (DMH) via tonic (ceaseless) inhibitory signaling. Although many POA neuronal cell bodies express a glutamatergic messenger RNA marker, their axons in the DMH predominantly release γ-aminobutyric acid (GABA), and their GABAergic terminals are increased by chronic heat exposure. These findings demonstrate that tonic GABAergic inhibitory signaling from POA neurons is a fundamental determinant of body temperature for thermal homeostasis and fever.
视前区（POA）体温调节中枢的双向控制器尚不清楚。在这里，我们使用大鼠鉴定出前列腺素 EP3 受体表达的 POA 神经元（POA 神经元）作为中枢体温调节机制中的关键双向控制器。POA 神经元在环境温度升高时被激活，但被发热介质前列腺素 E 抑制。在室温下化学遗传刺激 POA 神经元可通过增强散热来降低体温，而抑制它们则会引发涉及棕色脂肪产热的发热，类似于发热。POA 神经元通过持续（不断）抑制性信号传递至下丘脑背内侧核（DMH）中的交感兴奋神经元。尽管许多 POA 神经元胞体表达谷氨酸信使 RNA 标记物，但它们在 DMH 中的轴突主要释放γ-氨基丁酸（GABA），并且慢性热暴露会增加其 GABA 能末梢。这些发现表明，来自 POA 神经元的持续 GABA 能抑制性信号传递是体温平衡和发热的基本决定因素。
